The present invention relates to a method of screening a sample for the presence of one or more known compounds of interest, a method of mass spectrometry and a mass spectrometer.
Tandem mass spectrometry (MS/MS) is the name given to the method of mass spectrometry wherein parent or precursor ions generated from a sample are selected by a first mass filter/analyser and are then passed to a collision cell wherein they are fragmented by collisions with neutral gas molecules to yield daughter or product ions. The fragment or daughter ions are then mass analysed by a second mass filter/analyser and the resulting fragment or daughter ion spectra can be used to determine the structure and hence identify the parent or precursor ion. Tandem mass spectrometry is particularly useful for the analysis of complex mixtures such as biomolecules since it avoids the need for chemical clean-up prior to mass spectral analysis.
A common requirement is to screen and quantify a particular sample for unwanted contamination, often to ensure compliance with government legislation. A wide variety of matrixes and contaminants are often searched. For example, tests may be carried out for pesticides, markers relating to the place of origin of food, food safety (biological and chemical), peptides/proteins and environmental contaminants (e.g. water contamination from industrial processes). Such tests are commonly performed using tandem quadrupole instruments. However, as the requirement for the number of compounds to be screened increases then the duty cycle decreases. In addition, it is common now to require multiple fragment ions from a parent or precursor ion as further confirmation of the presence of the targeted compounds. Also, it is desirable to be able to re-examine the data for possible co-eluting interferences. Often the screen is performed in two stages. An acquisition is first performed using a Time of Flight mass spectrometer that searches for the required compounds on the basis of the accurate mass or mass to charge ratio of the parent ion from the compound. If the compound if found then the compound is confirmed and quantified using Multiple Reacting Monitoring (“MRM”) using a tandem quadrupole instrument.
Another type of mass spectrometer referred to as a hybrid quadrupole-Time of Flight mass spectrometer is known wherein the second quadrupole mass filter/analyser is replaced by an orthogonal acceleration Time of Flight mass analyser.
It is known that these types of mass spectrometers when used to perform conventional methods of obtaining fragment or daughter ion spectrum of a candidate parent or precursor ion suffer from low duty cycles which render them unsuitable for use in applications which require a higher duty cycle such as on-line chromatography applications.
It is also known that the duty cycle of a hybrid quadrupole-Time of Flight mass spectrometers may be improved significantly by cycling the collision device between a fragmenting mode of operation and a non-fragmenting mode of operation.
Hybrid quadrupole-Time of Flight mass spectrometers are also known have incorporated ion mobility separation devices within them allowing a further degree of selectivity based upon size shape and charge of the ion.
It is desired to improve known methods of screening a sample for known compounds.